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Sökning: onr:"swepub:oai:lup.lub.lu.se:a8cefef2-1c9c-4a37-bf1e-0e1fcd869bc5" > Proteomic analysis ...

Proteomic analysis of breast tumors confirms the mRNA intrinsic molecular subtypes using different classifiers : A large-scale analysis of fresh frozen tissue samples

Waldemarson, Sofia, (författare)
Lunds universitet, Lund University, Lunds Tekniska Högskola, Faculty of Engineering, LTH, Institutioner vid LTH, Departments at LTH, Institutionen för Immunteknologi, Department of Immunotechnology
Kurbasic, Emila, (författare)
Lunds universitet, Lund University, Lunds Tekniska Högskola, Faculty of Engineering, LTH, Institutioner vid LTH, Departments at LTH, Institutionen för Immunteknologi, Department of Immunotechnology
Krogh, Morten, (författare)
Amber Biosciences AB
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Cifani, Paolo, (författare)
Lunds universitet, Lund University, Lunds Tekniska Högskola, Faculty of Engineering, LTH, Institutioner vid LTH, Departments at LTH, Institutionen för Immunteknologi, Department of Immunotechnology
Berggård, Tord, (författare)
Novo Nordisk A/S
Borg, Åke, (författare)
Lunds universitet, Lund University, Medicinska fakulteten, Faculty of Medicine, Institutionen för kliniska vetenskaper, Lund, Department of Clinical Sciences, Lund, Sektion V, Division V, Onkologi och Patologi, MV, Oncology and Pathology, MV, Strategiska forskningsområden, Strategic Research Areas, BioCARE: Biomarkers in Cancer Medicine improving Health Care, Education and Innovation, BioCARE: Biomarkers in Cancer Medicine improving Health Care, Education and Innovation, Starka forskningsmiljöer, Strong Research Environments
James, Peter, (författare)
Lunds universitet, Lund University, Lunds Tekniska Högskola, Faculty of Engineering, LTH, Institutioner vid LTH, Departments at LTH, Institutionen för Immunteknologi, Department of Immunotechnology, University of Turku
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Lunds universitet Institutionen för Immunteknologi. (creator_code:org_t)
Lunds universitet Onkologi och Patologi, MV. (creator_code:org_t)
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Lunds universitet BioCARE: Biomarkers in Cancer Medicine improving Health Care, Education and Innovation. (creator_code:org_t)
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2016
Engelska.
Ingår i: Breast Cancer Research. - BioMed Central. - 1465-5411. ; 18:1
  • Tidskriftsartikel (refereegranskat)
Abstract Ämnesord
Stäng  
  • Background: Breast cancer is a complex and heterogeneous disease that is usually characterized by histological parameters such as tumor size, cellular arrangements/rearrangments, necrosis, nuclear grade and the mitotic index, leading to a set of around twenty subtypes. Together with clinical markers such as hormone receptor status, this classification has considerable prognostic value but there is a large variation in patient response to therapy. Gene expression profiling has provided molecular profiles characteristic of distinct subtypes of breast cancer that reflect the divergent cellular origins and degree of progression. Methods: Here we present a large-scale proteomic and transcriptomic profiling study of 477 sporadic and hereditary breast cancer tumors with matching mRNA expression analysis. Unsupervised hierarchal clustering was performed and selected proteins from large-scale tandem mass spectrometry (MS/MS) analysis were transferred into a highly multiplexed targeted selected reaction monitoring assay to classify tumors using a hierarchal cluster and support vector machine with leave one out cross-validation. Results: The subgroups formed upon unsupervised clustering agree very well with groups found at transcriptional level; however, the classifiers (genes or their respective protein products) differ almost entirely between the two datasets. In-depth analysis shows clear differences in pathways unique to each type, which may lie behind their different clinical outcomes. Targeted mass spectrometry analysis and supervised clustering correlate very well with subgroups determined by RNA classification and show convincing agreement with clinical parameters. Conclusions: This work demonstrates the merits of protein expression profiling for breast cancer stratification. These findings have important implications for the use of genomics and expression analysis for the prediction of protein expression, such as receptor status and drug target expression. The highly multiplexed MS assay is easily implemented in standard clinical chemistry practice, allowing rapid and cheap characterization of tumor tissue suitable for directing the choice of treatment.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Cancer and Oncology (hsv//eng)

Nyckelord

Breast cancer
Mass spectrometry
Molecular subtyping
Proteomics
Transcriptomics

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